OP0273 CHARACTERISTICS OF PATIENTS WITH DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS IN FRANCE
Authors: S. Hecquet, A. Combier, A. Steelandt, M. Pons, D. Wendling, A. Moltó, C. Miceli Richard, Y. Allanore, J. Avouac
Journal: Annals of the Rheumatic Diseases (2022)

Background Recently, EULAR has proposed a definition of difficult-to-treat rheumatoid arthritis (D2TRA). However, descriptive data on D2TRA are scarce and only one Japanese publication details the D2TRA encountered in routine practice, no similar work has been done in Europe so far. Objectives To describe D2TRA patients encountered in France according to two definitions and evaluate their therapeutic responses to different targeted therapies. Methods We reviewed all patients with RA treated in day hospital at Cochin University Hospital between 2020 and 2021. We divided our population into two groups of patients, a D2TRA group and a non-D2TRA group. This division was made on the same population according to two different definitions of D2TRA, resulting in four patient groups. The first definition is the one proposed by EULAR (EULAR D2TRA) defining D2TRAs as RAs with failure of ≥2 b/tsDMARDs (with different mechanisms of action) after failing csDMARD therapy. The second defined as D2TRA patients who have failed at least two targeted therapies, without prejudging the mechanism of action (non-EULAR D2TRA). We analyzed clinical characteristics and evaluated their response to different targeted therapies. Disease activity was assessed using the DAS for 28 joints (DAS28) at the latest visit. Results In total, we included 320 patients, we identified 76 EULAR D2TRA patients (mean age 59 years, 87% female) with 244 of corresponding non-DTRA patients (mean age 60 years, 85% female) and 120 non-EULAR D2TRA patients (mean age 58.7 years, 87% female) with 200 of corresponding non-DTRA (mean age 61 years, 85% female). Compared to non-D2TRA patients, there were significantly more D2TRA patients from low socioeconomic backgrounds in both D2TRA groups. In the EULAR-D2TRA group, compared to the non-D2TRA, there were significantly more patients with diabetes (14% vs 6%, p=0.024). D2TRA patients in both groups had significantly more rheumatoid factor (RF), interstitial lung disease (ILD) and a higher DAS28 than non-D2TRA patients. No difference was noted regarding ACPA and erosions. We observed a lower proportion of remission in both D2TRA groups than in non-D2TRA group (21% in EULAR-D2TRA vs 34% in non-D2TRA, p=0.034 and 23% in non-EULAR D2TRA vs 36% in non-D2TRA, p=0.024). There were significantly fewer patients on Methotrexate in the non-EULAR D2TRA group compared to the non-D2TRA group (53% vs 64%, p=0.046). In the non-EULAR D2TRA group, there were significantly more patients in remission on Rituximab than on TNF inhibitors (41% vs 5%, p=0.0032). We did not observe a significant difference in achieving remission in patients on JAK inhibitors or IL-6 inhibitors in the two groups of D2TRA. Table 1. Clinical data of patients with D2TRA NON D2T RA n=200 NON-EULAR D2T RA n=120 p-value NON D2T RA n=244 EULAR D2T RA n=76 p-value Low socioeconomic level 69 (35) 61 (51) 0.005 91 (37) 39 (51) 0.032 TJC (0-28), mean (SD ) 3.4 (4.6) 4.9 (5.8) 0.0167 3.5 (4.5) 5.6 (6.5) 0.001 SJC (0-28), mean (SD ) 2.4 (3.1) 3.5 (4.3) 0.0067 2.6 (3.3) 3.5 (4.3) 0.0503 CRP in mg/dl, mean (SD ) 6 (9.5) 7 .5 (12.1) 0.2128 6.1 (9.9) 7.9 (12.3) 0.2060 DAS28CRP, mean (SD ) 3.2 (1.2) 3.6 (1.4) 0.0044 3.2 (1.3) 3.6 (1.4) 0.0052 Remission 71 (36) 28 (23) 0.024 83 (34) 16 (21) 0.034 RF positive, n (% ) 156 (78) 105 (88) 0.037 193 (79) 68 (89) 0.043 Anti-CCP positive, n (% ) 152 (76) 101 (84) 0.099 188 (77) 66 (87) 0.075 Erosion, n (% ) 114 (57) 69 (58) 1 138 (56) 46 (60) 0.596 Interstitial Lung Disease, n (% ) 16 (8) 19 (16) 0.041 17 (7) 18 (24) &lt;0.001 Corticosteroids, n (% ) 84 (42) 64 (53) 0.064 101 (41) 46 (61) 0.004 Dose (mg), mean ± SD 6 (4.9) 5.5 (3.4) 0.416 6 (4.6) 5.3 (3.6) 0.374 Methotrexate, n (% ) 128 (64) 63 (53) 0.046 149 (61) 42 (55) 0.422 Dose (mg), mean ± SD 17.3 (4.25) 17.5 (5.3) 0.786 17.2 (4.5) 18.1 (5.1) 0.291 Conclusion The complexity of managing RA patients can be explained by socio-economic status and the presence of comorbidities such as diabetes and ILD. Our work suggests that D2TRA patients have less Methotrexate and better response to Rituximab. These data need to be confirmed in prospective studies to allow personalized management of D2TRA. Disclosure of Interests None declared